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ABSTRACT: Shaped pulses designed for broadband excitation, inversion and refocusing are important tools in modern NMR spectroscopy to achieve robust pulse sequences especially in heteronuclear correlation experiments. A large variety of mostly computer-optimized pulse shapes exist for different desired bandwidths, available rf-field strengths, and tolerance to B1-inhomogeneity. They are usually derived for a single spin 1/2, neglecting evolution due to J-couplings. While pulses with constant resulting phase are selfcompensated for heteronuclear coupling evolution as long as they are applied exclusively on a single nucleus, the situation changes for concurrently applied pulse shapes. Using the example of a (1)H,(13)C two spin system, two J-compensated pulse pairs for the application in INEPT-type transfer elements were optimized: a point-to-point pulse sandwich called BEBE(tr), consisting of a broadband excitation and time-reversed excitation pulse, and a combined universal rotation and point-to-point pulse pair called BUBI, which acts as a refocusing pulse on (1)H and a corresponding inversion pulse on (13)C. After a derivation of quality factors and optimization protocols, a theoretical and experimental comparison with conventionally derived BEBOP, BIBOP, and BURBOP-180° pulses is given. While the overall transfer efficiency of a single pulse pair is only reduced by approximately 0.1%, resulting transfer to undesired coherences is reduced by several percent. In experiments this can lead to undesired phase distortions for pairs of uncompensated pulse shapes and even differences in signal intensities of 5-10% in HSQC and up to 68% in more complex COB-HSQC experiments.
Journal of Magnetic Resonance 04/2013; 232C:7-17. · 2.14 Impact Factor
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ABSTRACT: Deuterium NMR imaging was used to evaluate the spatial distribution of the degree of alignment in different types of alignment media by monitoring the deuterium quadrupolar splitting using spatially resolved NMR techniques in conventional liquid state NMR instruments. These images allow the unambiguous distinction of magnetic field and alignment inhomogeneities present in partially aligned samples, revealing the underlying reasons for linebroadening within an alignment medium that cannot be explained by the sole analysis of 1D (2) H NMR spectra. For example, alignment inhomogeneities due to broken gels or the presence of concentration gradients in liquid crystalline solutions are clearly detected by the imaging methods proposed in this work.
Chemistry 04/2013; · 5.93 Impact Factor
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ABSTRACT: We present highly robust, optimal control-based shaped pulses designed to replace all 90° and 180° hard pulses in a given pulse sequence for improved performance. Special attention was devoted to ensuring that the pulses can be simply substituted in a one-to-one fashion for the original hard pulses without any additional modification of the existing sequence. The set of four pulses for each nucleus therefore consists of 90° and 180° point-to-point (PP) and universal rotation (UR) pulses of identical duration. These 1ms pulses provide uniform performance over resonance offsets of 20kHz ((1)H) and 35kHz ((13)C) and tolerate reasonably large radio frequency (RF) inhomogeneity/miscalibration of ±15% ((1)H) and ±10% ((13)C), making them especially suitable for NMR of small-to-medium-sized molecules (for which relaxation effects during the pulse are negligible) at an accessible and widely utilized spectrometer field strength of 600MHz. The experimental performance of conventional hard-pulse sequences is shown to be greatly improved by incorporating the new pulses, each set referred to as the Fantastic Four (Fanta4).
Journal of Magnetic Resonance 12/2012; 228C:16-31. · 2.14 Impact Factor
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ABSTRACT: With polyurethane (PU), a novel alignment medium for organic solvents is introduced and characterized, which is very robust and easy to produce on a large scale. Linear PU already constitutes an elastomer gel with several solvents based on its ability to form hydrogen bonds. Covalent cross-linking of the polymer with accelerated electrons provides an alignment medium with different properties. However, PU exhibits a number of undesired polymer signals in corresponding spectra, which ideally have to be removed spectroscopically. Within this context, we demonstrate the applicability of diffusion-filtered experiments for removal of the polymer signals. Example spectra for the usefulness of PU alignment media are provided for the common test molecules strychnine and norcamphor. Copyright © 2012 John Wiley & Sons, Ltd.
Magnetic Resonance in Chemistry 12/2012; 50 Suppl 1:S22-8. · 1.44 Impact Factor
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ABSTRACT: Robust experiments that cover a wide range of chemical shift offsets and J-couplings are highly desirable for a multitude of applications in small molecule NMR spectroscopy. Many attempts to improve individual aspects of the robustness of pulse sequence elements based on rational and numerical design have been reported, but a general optimization strategy to cover all necessary aspects for a fully robust sequence is still lacking. In this article, a viable optimization strategy is introduced that covers a defined range of couplings, offsets, and B(1) -field inhomogeneities (COB) in a time-optimal way. Individual components of the optimization strategy can be optimized in any adequate way. As an example for the COB approach, we present the (1) H - (13) C-COB-INEPT with transfer of approximately 99% over the full carbon and proton bandwidth and (1) J(CH) -couplings in the range of 120-250 Hz, which have been optimized using efficient algorithms derived from optimal control theory. The theoretical performance is demonstrated in a number of corresponding COB-HSQC experiments. Copyright © 2012 John Wiley & Sons, Ltd.
Magnetic Resonance in Chemistry 12/2012; 50 Suppl 1:S63-72. · 1.44 Impact Factor
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ABSTRACT: The configurational analysis of organic compounds is an important application for high resolution NMR spectroscopy. In the present study, a tetra-substituted pyrrolidine with four chiral carbon atoms is analyzed using classical methods based on (3) J and NOE data in solution and compared and verified with recently introduced alternative approaches via residual dipolar couplings (RDCs) in two weak anisotropic alignment media. The molecule shows sufficient rigidity in the five-membered ring for the configurational characterization with the various techniques. However, the flexibility caused by the many freely rotating bonds potentially poses problems for the interpretation of data. It is shown that RDCs measured in poly-γ-benzyl-l-glutamate and a stretched polydimethylsiloxane gel provide useful information for the distinction of diastereomers, but the success varies with the data interpretation strategy used. Although a general improvement of corresponding correlation factors is observed when limiting data to a subset of dipolar couplings directly connected to the central ring, the distinction power is reduced because of the smaller number of RDCs available for potential model falsification. Singular value decomposition for fitting experimental RDCs is able to distinguish in most cases the correct from incorrect configurations, but the differences in correlation factors can be relatively small. Surprisingly, predicting RDCs using the rod model as implemented in PALES gives best results in distinguishing the eight possible diastereomers. It is also found that the use of proton-phosphorus and carbon-phosphorus RDCs helps with the configurational analysis of the model compound. Copyright © 2012 John Wiley & Sons, Ltd.
Magnetic Resonance in Chemistry 12/2012; 50 Suppl 1:S92-S101. · 1.44 Impact Factor
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ABSTRACT: 90° and 180° universal rotation (UR) pulses are two of the most important classes of pulses in modern NMR spectroscopy. This article presents a systematic study characterizing the achievable performance of these pulses as functions of bandwidth, pulse length, and tolerance to B(1)-field inhomogeneity/miscalibration. After an evaluation of different quality factors employed in pulse design algorithms based on optimal control theory, resulting pulses are discussed in detail with a special focus on pulse symmetry. The vast majority of resulting BURBOP (broadband universal rotations by optimal control) pulses are either fully symmetric or have one symmetric and one antisymmetric Cartesian rf component, where the importance of the first symmetry has not been demonstrated yet and the latter one matches the symmetry that results from a previously derived construction principle of universal rotation pulses out of point-to-point pulses [3]. Optimized BURBOP pulses are shown to perform better than previously reported UR pulses, resulting in shorter pulse durations for the same quality of broadband rotations. From a comparison of qualities of effective universal rotations, we find that the application of a single optimal refocusing pulse matches or improves the performance of two consecutive inversion pulses in INEPT-like pulse sequence elements of the same total duration.
Journal of Magnetic Resonance 10/2012; · 2.14 Impact Factor
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Robert Berger,
Jacques Courtieu,
Roberto R Gil,
Christian Griesinger,
Matthias Köck,
Philippe Lesot, Burkhard Luy,
Denis Merlet,
Armando Navarro-Vázquez,
Michael Reggelin,
Uwe M Reinscheid,
Christina M Thiele,
Markus Zweckstetter
Angewandte Chemie International Edition 07/2012; 51(33):8388-91. · 13.45 Impact Factor
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ABSTRACT: Optimizing pulse performance often requires a compromise between maximizing signal amplitude and minimizing spectral phase errors. We consider methods for the de novo design of universal rotation pulses, applied specifically but not limited to refocusing pulses. Broadband inversion pulses that rotate all magnetization components 180° about a given fixed axis are necessary for refocusing and mixing in high-resolution NMR spectroscopy. The relative merits of various methodologies for generating pulses suitable for broadband refocusing are considered. The de novo design of 180° universal rotation pulses (180(UR)(°)) using optimal control can provide improved performance compared to schemes which construct refocusing pulses as composites of existing pulses. The advantages of broadband universal rotation by optimized pulses (BURBOP) are most evident for pulse design that includes tolerance to RF inhomogeneity or miscalibration. Nearly ideal refocusing is possible over a resonance offset range of ± 170% relative to the nominal pulse B(1) field, concurrent with tolerance to B(1) inhomogeneity/miscalibration of ± 33%. We present new modifications of the optimal control algorithm that incorporate symmetry principles (S-BURBOP) and relax conservative limits on peak RF pulse amplitude for short time periods that pose no threat to the probe. We apply them to generate a set of low-power 180(BURBOP)(°) pulses suitable for widespread use in (13)C spectroscopy on the majority of available probes. A quantitative measure for the reduced spectral phase error provided by these symmetry principles is also derived. For pulses designed according to this symmetry, refocusing phase errors are virtually eliminated upon application of EXORCYCLE or an equivalent G-180(S-BURBOP)(°)-G gradient sandwich, independent of resonance offset and RF inhomogeneity. The magnitude of the refocused component is not significantly compromised in achieving such ideal phase performance.
Journal of Magnetic Resonance 01/2012; 216:78-87. · 2.14 Impact Factor
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ABSTRACT: Broadband inversion pulses that rotate all magnetization components 180
degrees about a given fixed axis are necessary for refocusing and mixing in
high-resolution NMR spectroscopy. The relative merits of various methodologies
for generating pulses suitable for broadband refocusing are considered. The de
novo design of 180 degree universal rotation pulses using optimal control can
provide improved performance compared to schemes which construct refocusing
pulses as composites of existing pulses. The advantages of broadband universal
rotation by optimized pulses (BURBOP) are most evident for pulse design that
includes tolerance to RF inhomogeneity or miscalibration. We present new
modifications of the optimal control algorithm that incorporate symmetry
principles and relax conservative limits on peak RF pulse amplitude for short
time periods that pose no threat to the probe. We apply them to generate a set
of pulses suitable for widespread use in Carbon-13 spectroscopy on the majority
of available probes.
11/2011;
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Angewandte Chemie International Edition 09/2011; 50(40):9487-90. · 13.45 Impact Factor
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Angewandte Chemie International Edition 03/2011; 50(11):2643-5. · 13.45 Impact Factor
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ABSTRACT: In modern, high resolution NMR spectroscopy, anisotropic parameters play an important role. They can be measured with the help of liquid crystalline mesophases or stretched polymer gels as so-called alignment media. Biologically occurring chiral polymers are of special interest as alignment media for this technique because they allow enantiomers to be distinguished.
Biopolymers have been studied by deuterium 1D and J-BIRDd,X-HSQC NMR experiments with respect to their ability to distinguish enantiomers and a summary of existing biopolymers for the task is given.
Gelatin is shown to distinguish D-proline from L-proline and next to already known biopolymers, gellan gum is introduced as a novel biologically derived polymer that is able to partially align solute molecules.
Biologically occurring and biodegradable polymers are well suited as alignment media and in many cases are able to distinguish enantiomers. As the orienting properties are different for different media and solute molecules, the bandwidth of corresponding polymers will be further increased in the future.
The International journal of artificial organs 03/2011; 34(2):134-8. · 1.86 Impact Factor
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ABSTRACT: The successful measurement of anisotropic NMR parameters like residual dipolar couplings (RDCs), residual quadrupolar couplings (RQCs), or residual chemical shift anisotropy (RCSA) involves the partial alignment of solute molecules in an alignment medium. To avoid any influence of the change of environment from the isotropic to the anisotropic sample, the measurement of both datasets with a single sample is highly desirable. Here, we introduce the scaling of alignment for mechanically stretched polymer gels by varying the angle of the director of alignment relative to the static magnetic field, which we call variable angle NMR spectroscopy (VA-NMR). The technique is closely related to variable angle sample spinning NMR spectroscopy (VASS-NMR) of liquid crystalline samples, but due to the mechanical fixation of the director of alignment no sample spinning is necessary. Also, in contrast to VASS-NMR, VA-NMR works for the full range of sample inclinations between 0° and 90°. Isotropic spectra are obtained at the magic angle. As a demonstration of the approach we measure ¹³C-RCSA values for strychnine in a stretched PDMS/CDCl₃ gel and show their usefulness for assignment purposes. In this context special care has been taken with respect to the exact calibration of chemical shift data, for which three approaches have been derived and tested.
Journal of Magnetic Resonance 03/2011; 209(1):19-30. · 2.14 Impact Factor
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ABSTRACT: Perdeuterated poly(acrylonitrile) is introduced as a practically proton-free alignment medium for the measurement of anisotropic NMR parameters; its use in conventional glass tubes and in a Kalrez® 8002 UP-based stretching device with resulting spectra of astonishing quality are demonstrated.
Chemical Communications 09/2010; 46(43):8273-5. · 6.17 Impact Factor
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ABSTRACT: Residual dipolar couplings (RDCs) obtained in a stretched polydimethylsiloxane gel are applied to determine the 7-membered ring conformation in a 2-phenyl-3-benzazepine derivative, and to simultaneously assign all methylene proton pairs using only (1)D(CH) RDCs and DFT molecular modelling data.
Chemical Communications 08/2010; 46(32):5879-81. · 6.17 Impact Factor
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Chemistry 05/2010; 16(24):7087-9. · 5.93 Impact Factor
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ABSTRACT: Molecular conjugates comprising targeting ligands hold great promise for site-specific gene delivery to distant tumors and individual organs including the lung. Here we show that prostaglandin I2 analogues can be used to improve gene transfer efficiency of polyethylenimine (PEI) gene vectors on bronchial and alveolar epithelial cells in vitro and lungs of mice in vivo. Prostacyclin (IP1) receptor expression was confirmed in pulmonary epithelial cell lines by western blot. Iloprost (ILO) and treprostinil (TRP), two prostaglandin I2 analogues, were conjugated to fluorescein-labeled BSA (FLUO-BSA) and compared for IP1 receptor binding/uptake in different lung cell lines. Binding of FLUO-BSA-ILO was 2-4-fold higher than for FLUO-BSA-TRP and could be specifically inhibited by free ILO and IP1 receptor antagonist CAY10449. Internalization of FLUO-BSA-ILO was confirmed by confocal microscopy. Molecular conjugates of PEI and ILO (PEI-g-ILO) were synthesized with increasing coupling degree (F(ILO) (ILO:PEI) = 2, 5, 8, 16) and analyzed for DNA binding, particle formation and transfection efficiency. At optimized conditions (N/P 4, F(ILO) = 5), gene expression using PEI-g-ILO was significantly up to 46-fold higher than for PEI gene vectors and specifically inhibited by CAY10449. Gene expression in the lungs of mice after aerosol delivery was 14-fold higher with PEI-g-ILO F(ILO) = 5 than for PEI. We suggest that targeting of IP1 receptor using ILO represents a promising approach to improve pulmonary gene transfer.
Biomaterials 04/2010; 31(10):2903-11. · 7.40 Impact Factor
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ABSTRACT: Precise NMR structural determination of distinct hydrogen-bonded secondary folds in unnatural peptides is demonstrated by using residual dipolar couplings (RDCs), measured in organic solvent media. The results show that the conventional constraints, (3)J(HH) and NOE-derived distances alone do not allow the accurate structural elucidation even for rigid foldamers and emphasize the need of RDC-based structure validation and refinement for unnatural peptides in particular and small organic molecules in general.
Journal of the American Chemical Society 11/2009; 131(43):15590-1. · 9.91 Impact Factor
